The overarching goal of my research program is to gain an understanding of the molecular mechanisms that govern stem cell potency and how dysregulation of these mechanisms can contribute to disease onset and progression, including oncogenesis. My laboratory employs genetic, genomic, and single-cell analysis approaches in murine systems to address these fundamental questions, and, in parallel, utilizes human induced pluripotent cells and patient samples to translate findings into human systems. Using these approaches we have identified novel pathways underlying the somatic stem cell self-renewal and the ontogeny of hematopoietic and gastrointestinal cancers. These pathways are subsequently being assessed as potential points for therapeutic intervention in cancers and diseases of regenerative failure. We have also begun to unravel the hierarchical structure of the intestinal stem cell compartment with the ultimate goal of understanding how perturbations in this hierarchy contribute to disease states, including cancer, chronic inflammation, and regeneration in response to acute injuries such as ischemia or radiation damage.